Cloning and Expression of a Developmentally Regulated Protein That Induces Mitogenic and Neurite Outgrowth Activity

• DOI: 10.1126/science.2270483
• Publication Date: 2006-10-05T22:10:14Z
• Authors: Yue-Sheng Li; Peter G. Milner; Anil K. Chauhan; Mark A. Watson; Ruth M. Hoffman; Charles M. Kodner; Jeffrey Milbrandt; Thomas F Deuel
• Keywords: 0301 basic medicine; 0303 health sciences; Base Sequence; Molecular Sequence Data; Brain; Transfection; Axons; Cell Line; Rats; 3. Good health; 03 medical and health sciences; Organ Specificity; Sequence Homology, Nucleic Acid; Animals; Cytokines; Humans; Cattle; Amino Acid Sequence; Cloning, Molecular; Mitogens; Carrier Proteins; Cell Division

A heparin binding mitogenic protein isolated from bovine uterus shares NH 2 -terminal amino acid sequence with a protein isolated from newborn rat brain. The cDNA's of the bovine, human, and rat genes have been isolated and encode extraordinarily conserved proteins unrelated to known growth or neurotrophic factors, although identity of nearly 50 percent has been found with the predicted sequence of a retinoic acid induced transcript in differentiating mouse embryonal carcinoma cells. Lysates of COS-7 cells transiently expressing this protein were mitogenic for NRK cells and initiated neurite outgrowth from mixed cultures of embryonic rat brain cells. RNA transcripts encoding this protein were widely distributed in tissues and were developmentally regulated. This protein, previously designated as heparin binding growth factor (HBGF)-8, is now renamed pleiotrophin (PTN) to reflect its diverse activities. PTN may be the first member of a family of developmentally regulated cytokines.